Genetic Variant ADAMTS7:p.Arg1661Leu (chr15-78759500-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014272.5(ADAMTS7):c.4982G>T(p.Arg1661Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1661H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.156

Publications

1 publications found

Variant links:

Genes affected

ADAMTS7 (HGNC:223): (ADAM metallopeptidase with thrombospondin type 1 motif 7) The protein encoded by this gene is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family. Members of this family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and may regulate vascular smooth muscle cell (VSMC) migration. Mutations in this gene may be associated with susceptibility to coronary artery disease. [provided by RefSeq, Feb 2016]

ADAMTS7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS7	NM_014272.5	MANE Select	c.4982G>T	p.Arg1661Leu	missense	Exon 24 of 24	NP_055087.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS7	ENST00000388820.5	TSL:1 MANE Select	c.4982G>T	p.Arg1661Leu	missense	Exon 24 of 24	ENSP00000373472.4	Q9UKP4
ADAMTS7	ENST00000972106.1		c.4955G>T	p.Arg1652Leu	missense	Exon 24 of 24	ENSP00000642165.1
ADAMTS7	ENST00000972107.1		c.4922G>T	p.Arg1641Leu	missense	Exon 24 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000135

AC:

AN:

222514

AF XY:

0.0000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000759

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718874

African (AFR)

AF:

0.00

AC:

AN:

33346

American (AMR)

AF:

0.00

AC:

AN:

44276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.00

AC:

AN:

85358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109356

Other (OTH)

AF:

0.00

AC:

AN:

59748

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000167

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.097

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.51

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.6

PhyloP100

-0.16

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.19

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.41

MutPred

0.32

Loss of MoRF binding (P = 0.0287)

MVP

0.50

MPC

0.63

ClinPred

0.88

GERP RS

2.9

Varity_R

0.26

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over